In the Familial Atherosclerosis Treatment Study (FATS), the reduction in clinical events (75%) far outweighed the modest frequency and magnitude of lesion regression observed among those receiving intensive lipid-lowering therapy. To understand this result, the disruptive changes in plaque that trigger clinical events (cardiac death, myocardial infarction, unstable angina) are described. Data are presented in support of the idea that the clinical benefits of lipid-lowering therapy are best explained by stabilization, by depletion of lipid, of the "dangerous" subpopulation of lipid-rich plaques that are often associated with only mild or moderate coronary narrowing.